Genomics

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Down modulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma


ABSTRACT: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal overall survival (OS) and to date few molecular markers are available to guide patient management. This study aimed to identify a prognostic miRNA signature in MPM patients who did not undergo tumor resection. Whole miRNA profiling using a microarray platform was performed on 26 unresected MPM with distinct clinical outcome: 15 patients had aggressive disease (OS<12 months) and 11 patients indolent disease (OS>36 months). Three prognostic miRNAs (mir-99a, let-7c and miR-125b) encoded at the same cluster (21q21) were selected for further validation and tested on publicly available miRNA sequencing data (TCGA) from 72 MPM patients with survival data. A risk model was built based on these 3 miRNAs that was validated by quantitative PCR in an independent set of 30 MPM patients. High risk patients had shorter median OS (7.6 months) as compared with low-risk patients (median not reached). In the multivariate Cox model, a high risk score was an independently associated with shorter OS (HR=3.14; 95% CI, 1.18–8.34; P=0.022). Our study identified that the downregulation of the miR-99a/let-7/miR-125b miRNA cluster predicts poor outcome in unresected MPM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE92636 | GEO | 2017/07/28

SECONDARY ACCESSION(S): PRJNA358208

REPOSITORIES: GEO

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